Substance P is a protein naturally occurring in the body. It is a tachykinin which induces contraction of smooth muscle and appears in humans and other mammals at highest concentrations in brain, intestine, spinal ganglia.
Since the late 1970""s, studies have shown that Substance P has a variety of biological activities including acting as a vasodilator, stimulates salivation, can cause increased gut permeability. Of particular interest to the present invention is the observation that Substance P can, at different concentrations, cause analgesia or hyperalgesia. Although its biological activity can be difficult to measure, its activity as a systemic signal is highly stable at ambient and refrigerated temperatures.
Substance P can act as a neurotransmitter or a hormone (particularly in the gut as a hormone). The vasodilation caused by Substance P is a result of its direct inhibitory effect on arteriolar smooth muscle. This effect is mediated by receptors. that appear specific to Substance P versus other vasodialators. Of interest to the present invention is that those receptors appear to be identical to those specific for rubeola virus. While Substance P inhibits contraction of arteriolar smooth muscle, it stimulates contraction of intestinal, bronchial and venous smooth muscle. Substance P can also cause diuresis and natriuresis in kidneys. These observations suggest that there could be more than one type of Substance P receptor.
The present invention relates to the observation that Substance P appears to be a signal for the mediation of neurogenic pain and that it would appear to be a candidate as a therapeutic agent for those types of pain which are most difficult to control, especially peripheral neuropathy.
The present invention provides methods for treatment of disease states selected from the group consisting of respiratory dysfunction and pain comprising administration of an effective amount of Substance P. The invention also provides pharmaceutical compositions for treatment of respiratory dysfunction and pain comprising an effective amount of Substance P in combination with a suitable carrier.
It is believed that Substance P may function in the treatment of pain by having a direct effect on pain receptors. Moreover, while not wishing to be bound by any particular theory of the invention, Substance P may operate in treatment of certain respiratory conditions such as Reactive Upper Airway Dysfunction (RUDS) through a mechanism of treatment of neuropathy. Specifically, RUDS has been described as a cranial nerve neuropathy involving the 10th cranical nerve (vagus). Accordingly, it may be that Substance P treats respiratory conditions such as RUDS through a mechanism which treats neuropathies associated with those diseases.
An effective amount of Substance P according to the invention is an amount which results in a reduction in the symptoms of a respiratory disease or of pain symptoms. Amounts of Substance P ranging from 10xe2x88x927 to 10xe2x88x922 mg are contemplated to be effective according to the invention. While preferred dosages include those ranging from 10xe2x88x925 to 10xe2x88x924 mg Substance P and 8xc3x9710xe2x88x925 mg has been found to be particulary effective when administered from one to six times daily in the form of sublingual drops, those of ordinary skill would be capable of adjusting the dosage amounts and schedule by observation of the effectiveness of treatment. Accordingly, it is contemplated that the range in dosage for the application could be several logs higher or lower than the optimum above. While the preferred route of administration is sublingual administration, it would be apparent to those of skill in the art that other routes would also be suitable for treatment according to the invention including subcutaneous administration, intramuscular, intravenous administration and the like. The invention also provides pharmaceutical compositions for treatment of respiratory conditions and pain comprising Substance P in combination with a suitable carrier such as saline or other pharmaceutically acceptable excipients.